【作者】 邱晓頔；

【导师】 龚岚；

【作者基本信息】 复旦大学 ， 眼科学， 2009， 硕士

【摘要】 干眼是由于各种原因引起的泪液以及角结膜上皮损伤的慢性疾患,病因较为复杂,临床上极易误诊。干眼诊断标准的精确性及诊断方法的变异性均是造成误诊的主要原因。因此,寻找一种可重复性好、操作便捷的的干眼诊断方法显得尤为重要。随着光学相干断层成像术(optical coherence tomography,OCT)在眼前节应用的拓展及技术的进一步发展,第四代傅立叶域(Fourier domain,FD)OCT所具有的高分辨率、高速度等一系列的特点超越了以往的时域(Time domain,TD)OCT,其所具有的高分辨率眼前节成像功能使其在泪河(tear meniscus)测量方面的应用引起了研究者的广泛关注,但目前尚未有关于第四代傅立叶域OCT在诊断干眼上的效力及正常人泪河方面的研究。因此,本研究对第四代傅立叶域前节OCT应用于泪河成像及测量进行研究,选择了不同年龄段、不同类型干眼患者,同时选择正常人作为对照,探讨第四代傅立叶域前节OCT测量泪河在诊断干眼方面的作用,明确傅立叶域前节OCT应用于何种干眼症类型具有更高的诊断效力;同时对正常对照组按照年龄进行分组,以研究正常人泪河生理值的年龄变化规律。研究结果表明,第四代傅立叶域前节OCT能够对泪河横截面进行清晰成像并进行精确测量,与临床诊断干眼的检查方法(BUT、Schirmer试验)存在良好的诊断一致性,能够直观的反映泪河情况。作为一种无创非接触性、操作简单的检查方法,第四代傅立叶域前节OCT在干眼诊断尤其是水液缺乏型干眼的诊断方面具有良好的应用前景。第一部分傅立叶域前节OCT在泪河成像及测量的应用研究目的研究第四代傅立叶域前节OCT(FD-OCT)应用于泪河成像及测量方面的作用。方法选择我院门诊主诉符合干眼的146例(146眼)患者,同时选取正常志愿者160例(160眼)进行对照,采用傅立叶域(Fourier domain)技术的OCT(RTVue-100)对全部入组者进行泪河高度(TMH)、泪河深度(TMD)及泪河横截面面积(TMA)的测量,结合BUT、角膜荧光素染色及Schirmer试验,并对入组者进行《干眼量表》的评分,对傅立叶域前节OCT泪河成像及测量泪河生理值的可重复性进行分析。结果干眼组的TMH、TMD、TMA平均值分别为232.319±17.549(μm)、151.494±12.811(μm)、0.024428±0.003712(mm~2),正常对照组TMH、TMD、TMA平均值分别为328.113±19.036(μm)、220.906±12.935(μm)、0.045618±0.005623(mm~2)。干眼组泪河各数值均明显小于正常对照组,差异具有统计学意义(TMHt=12.2646,P=0.0000,TMD t=12.0567,P=0.0000,TMA t=10.1556,P=0.0000)。对两组的个体间变异度进行分析的结果显示,干眼组其泪河测量数值的变异度相对较小,而正常对照组的泪河测量值变异度相对较大。对两组的OCT测量可重复性进行分析的结果显示,两组数值的个体内变异度均较小,说明第四代傅立叶域OCT测量泪河的可重复性良好。干眼组及正常对照组的OCT图像在泪河边界线、泪河横截面积、泪液透明度等方面有较大的差别。结论第四代傅立叶域OCT能够对泪河横截面进行清晰成像并进行精确测量,可重复性好,能够直观的反映泪河情况。干眼患者泪河测量值明显小于正常对照组,在OCT图像上也与正常组有较大差别。第二部分正常人群的泪河生理值及其年龄变化规律目的采用第四代傅立叶域前节OCT(FD-OCT)观察泪河的相关年龄变化及评价FD-OCT在干眼诊断方面的作用。方法选择干眼患者146例(146眼)及正常志愿者160例(160眼)进行对照,按年龄分为四组:A组(0-19岁),B组(20-39岁),C组(40-59岁),D组(大于60岁);干眼患者各组人数依次为6,60,60,20人,正常对照各组人数依次20,60,60,20人。采用傅立叶域(Fourier domain)技术的第四代高分辨率OCT(RTVue-100)对全部入组者进行泪河高度(TMH)、泪河深度(TMD)及泪河横截面面积(TMA)的测量,结合BUT、角膜荧光素染色及Schirmer试验,并对入组者进行《干眼量表》评分。对上述检查结果的相关性进行分析,得出各年龄段的泪河生理值,绘制ROC曲线,进一步评价第四代傅立叶域前节OCT在诊断干眼方面的应用。结果对临床检查结果进行spearman相关分析结果显示泪河的各个数值均与个体的症状及临床检查结果存在一定的相关性。干眼组临床检查结果、泪河测量值均与正常对照组之间存在较大的差异。泪河各数值与年龄呈负相关关系(TMH r=—0.0649,p=0.000,TMD r=—0.0299,p=0.0024,TMA r=—0.0320,p=0.0017)。OCT正确诊断干眼的总体比例分别为TMH 68.95%、TMD 70.59%、TMA 70.92%。各年龄段的正确诊断比例亦不相同。ROC曲线下面积(AUC)总体结果显示,TMH为0.7337,TMD为0.7477,TMA为0.7461。各年龄段的AUC之间存在一定的差异。总体诊断界值TMH为259(μm),TMD为165.6667(μm),TMA为0.024(mm~2),各组诊断界值随年龄的增大而下降。结论第四代傅立叶域前节OCT能够直观的反映泪河生理值的相关年龄变化,与临床诊断干眼的检查方法(BUT、Schirmer试验)存在较好的诊断一致性,各年龄段的诊断效力与诊断界值存在一定的差异。第三部分傅立叶域前节OCT在干眼症诊断方面的作用目的采用第四代傅立叶域前节OCT(FD-OCT)测量各类型干眼症患者泪河数值,评价其在干眼诊断方面的作用。方法选择干眼(DE组)患者146例(146眼),单纯水液缺乏型干眼(ATD组)患者102例(102眼),单纯脂质缺乏型干眼(LTD组)患者81例(81眼),Sj(o|¨)gren综合征(SS组)患者53例(53眼),同时选择正常对照(N组)160例(160眼)进行比较。采用傅立叶域(Fourier domain)技术的第四代高分辨率OCT(RTVue-100)对全部入组者进行泪河高度(TMH)、泪河深度(TMD)及泪河横截面面积(TMA)的测量,结合BUT、角膜荧光素染色及Schirmer试验,并对入组者进行《干眼量表》评分。绘制ROC曲线,评价第四代傅立叶域前节OCT在诊断各类型干眼方面的应用。结果对临床检查结果进行数据分析显示,各组的各项数据平均值之间存在较大差异。对各组的诊断效力进行分析的结果显示,SS组诊断效力最高,TMH91.19%、TMD 92.51%、TMA92.51%:LD组最低,TMH45.49%、TMD67.06%、TMA46.27%;DE组与ATD组相似。计算TMA的ROC曲线下面积(AUC)结果显示,DE组为0.7855,AD组为0.7110,LD组为0.5279,SS组为0.9706。结论第四代傅立叶域OCT能够精确测量各种类型干眼症的泪河数据,与临床诊断干眼的检查方法(BUT、Schirmer试验)存在良好的诊断一致性。作为一种无创非接触性、操作简单的检查方法,第四代傅立叶域前节OCT在干眼诊断尤其是水液缺乏型干眼的诊断方面具有良好的应用前景。更多还原

【Abstract】 Dry eye is caused by a variety of reasons,as well as tear deficiency,corneal or conjunctival epithelial damage as chronic disorders.The cause is more complex, clinically misdiagnosed easily.The reproducibility of dry eye diagnostic criteria is not satisfied and there are many factors to interfere the results.So it is very important to search for a rapid and reliable method for diagnosis of dry eye.With the development of optical coherence tomography(optical coherence tomography,OCT) and further application in anterior segment,the fourth-generation Fourier domain(Fourier domain) OCT has beyond the characteristics of the previous time-domain(Time domain) OCT with high resolution and high speed.It has led to widespread concern researchers with a high-resolution functional imaging of anterior segment of tear meniscus.However, there is no research on the effectiveness of the Fourier-domain OCT in the diagnosis of dry eye and normal tear meniscus area.Therefore,this study will probe on the diagnostic effectiveness and tear meniscus imaging of fourth-generation Fourier domain OCT.We enroll in different ages,different types of dry eye patients,as well as normal controls to explore diagnostic effectiveness of Fourier domain OCT,in order to identify the type of dry eye which has a higher diagnostic effect.At the same time,we make the normal control group into Sub-groups in accordance with age to investigate age-related variations of human tear meniscus in Chinese.The results show that the fourth generation Fourier domain OCT can clearly image and measure the cross-sectional tear meniscus.It also has a good consistency with clinical diagnosis of dry eye examination(BUT,Schirmer test).As a non-invasive,non-contact,simple screening method,the fourth generation Fourier-domain OCT has a good application prospects in the diagnosis of dry eye,especially in aqueous tear deficiency. PartⅠResearch on the tear meniscus imaging and measurement of the anterior segment Fourier domain OCTObjective To discuss the utilization of the fourth generation anterior segment Fourier domain optical coherence tomography in the imaging and measurement of tear meniscusMethods We enrolled 146 cases(146 eyes) and 160 controls(160 eyes) in this study. The tear meniscus height(TMH),tear meniscus depth(TMD) and tear meniscus area (TMA) of each participant were measured by Fourier domain OCT(RTVue-100).We also estimated the tear break up time(BUT),performed the cornea fluorescein staining and Schirmer test,and recorded score of the dry eye questionnaire.The variability of the fourth generation anterior segment Fourier domain OCT in tear meniscus imaging and measurement was discussed.Results The average values of TMH,TMD and TMA in the patient group were 232.319±17.549(μm)、151.494±12.811(μm)、0.024428±0.003712(mm2), comparing with 328.113±19.036(μm)、220.906±12.935(μm)、0.045618±0.005623(mm2) in the control group,the difference of which reached significant (TMH t=12.2646,P=0.0000,TMD t=12.0567,P=0.0000,TMA t=10.1556, P=0.0000).The individual variability of the TMH,TMD and TMA in the patient group was less than the control group.The repeatability analysis showed a small variation in measurement.The OCT images of the bound and cross section area of the tear meniscus and the clarity of the tear fluid in the patient group were obviously different from those in the control group.Conclusion The fourth generation Fourier domain anterior segment optical coherence tomography can clearly image and measure the cross section of tear meniscus,the result of which showed a good coherence with the traditional diagnostic test(BUT,Schirmer test) and directly reflect features of the tear meniscus. PartⅡAge-Related Variations of Human Tear Meniscus in ChineseObjective To investigate age-related variations of human tear meniscus in Chinese and diagnosis of dry eye using Fourier domain anterior segment OCT.Methods.We enrolled 146 cases(146 eyes) and 160 controls(160 eyes) in this study.All the subjects in these two groups were divided into four subgroups according to different ages,respectively,group A(0～19),group B(20～39),group C (40～59) and group D(over 60).Dry eye patients have 6,60,60,20 in each group, normal controls have 6,60,60,20 in each group.The tear meniscus height(TMH),tear meniscus depth(TMD) and tear meniscus area(TMA) of each participant were measured by Fourier domain OCT(RTVue-100).We also estimated the tear break up time(BUT),performed the cornea fluorescein staining and Schirmer test,and recorded score of the dry eye questionnaire.The relativity of the clinical examinations was tested,the tear meniscus of the two groups were measured and ROC curves were drawn.Results There is a significant correlation among tear meniscus values,individual syndrome and clinical diagnoses.The mean TMH、TMD、TMA for dry-eye patients were significantly lower than those for control groups.There was negative correlation between tear meniscus values and age for Chinese healthy subjects(TMH r=-0.0649,p=0.000,TMD r=-0.0299,p=0.0024,TMA r=-0.0320,p=0.0017).The accuracy of the diagnosis of dry eye by Fd-OCT was TMH 68.95%、TMD 70.59%、TMA 70.92%.It’s different between the age sub-groups.Area under the ROC curve (AUC) showed that overall,TMH to 0.7337,TMD is 0.7477,TMA is 0.7461.AUC of all ages there are some differences between.TMH Diagnostic value of the overall community for the 259(μm),TMD for 165.6667(μm),TMA was 0.024(mm2),the diagnosis of all ages increase community values decline with age.Conclusions Fd-OCT could instantly imply the age-related variations of human tear meniscus and has good consistency with the clinical diagnose examinations.It has different diagnostic accuracy in each age sub-group. PartⅢThe utilization of the fourth generation Fourier domain anterior segment OCT(FD-OCT) in the diagnosis of dry eyeObjective To discuss the utilization of the fourth generation anterior segment Fourier domain OCT in the diagnosis of different types of dry eye patients.Methods We enrolled 146 cases(146 eyes)of dry eye patients(DE group),102 cases(102 eyes)of aqueous tear deficiency patients(ATD group),81 cases(81 eyes)of lipid tear deficiency patients(LTD group),53 cases(53 eyes)of Sj(o|¨)gren syndrome patients(SS group)and 160 controls(160 eyes) in this study.The tear meniscus height (TMH),tear meniscus depth(TMD) and tear meniscus area(TMA) of each participant were measured by Fourier domain OCT(RTVue-100).We also estimated the tear break up time(BUT),performed the cornea fluorescein staining and Schirmer test,and recorded score of the dry eye questionnaire.The relativity of the clinical examinations was tested,the tear meniscus of the two groups were measured and ROC curves were drawn.Results The average values of clinical measurements in the patient group were quite different.The results of the diagnostic effectiveness for each group showed,SS group had the highest diagnostic effectiveness,TMH 91.19%,TMD 92.51%,TMA 92.51%; LD group had the lowest,TMH 45.49%,TMD 67.06%,TMA 46.27%.DE group was almost the same with ATD group.The area under the ROC curve(AUC) of TMA showed,DE group was 0.7855,AD group was 0.7110,LD group was 0.5279,SS group was 0.9706.Conclusion The fourth generation Fourier domain anterior segment optical coherence tomography can accurately measure all types of dry eye tears meniscus,, the result of which showed a good coherence with the traditional diagnostic test(BUT, Schirmer test) and directly reflect features of the tear meniscus.As a non-traumatic and non-contact technique,the fourth generation Fourier domain anterior segment OCT has a favorable prospect in the diagnosis of dry eye,especially in aqueous tear deficiency.更多还原